Outcome after kidney transplantation in children with thrombotic risk factors

BACKGROUND: According to the data from the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS), vascular thrombosis accounts for 11.6% of graft losses in pediatric renal transplantation. In adults, inherited and acquired thrombophilic risk factors, e.g. factor V Leiden mutation, have been associated with early graft loss and increased rejection episodes. Data on the impact of these factors on the outcome of children after renal transplantation are rare. METHODS/PATIENTS: Sixty-six pediatric patients awaiting renal transplantation (mean age 10.1 yr) were screened for inherited and acquired risk factors for hypercoagulable disorders (protein C, S, and antithrombin III deficiency, antiphospholipid antibodies, factor V Leiden, prothrombin, and MTHFR mutation) in order to intensify anticoagulation in those with an increased risk for thrombophilia: intravenous heparin was administered with a partial prothrombin time (PTT) prolongation of 50 s for 14 days and switched to low-molecular-weight heparin for another 8 wk before aspirin was introduced for the first year. Patients without hypercoagulable risk factors were treated with heparin without PTT prolongation for 14 days and switched to aspirin immediately afterwards. The results on graft survival, incidence of acute rejection episodes, and long-term renal graft function were analyzed between recipients with and without hypercoagulable risk factors. RESULTS: Thrombophilic risk factors were identified in 27.3% of our patients. No thrombosis occurred. One serious bleeding complication led to a second surgical intervention. The rate of acute rejection episodes was not increased in patients with and without thrombotic risk factors after 90 days (16.7 vs. 25%), 1 yr (22.2 vs. 33.3%), and 3 yr (38.9 vs. 41.7%) of follow-up, respectively (p = n.s.). After a mean follow-up of 3 yr the kidney function was comparable in both groups, with 63.1 in recipients with and 69.8 mL/min/1.73 m(2) in recipients without hypercoagulable risk (p = n.s.). At latest follow-up, three graft losses were found not to be attributed to thrombotic risk factors. INTERPRETATION: Children with thrombophilic risk factors were identified and treated with an intensified anticoagulation regimen after renal transplantation. An increased risk for graft failure, acute rejection episodes, or impaired renal function for pediatric renal transplant recipients with hypercoagulable status was not found.     

Pretransplant peritoneal dialysis and graft thrombosis following pediatric kidney transplantation: a NAPRTCS report

Graft thrombosis is a common cause of graft failure in pediatric renal transplantation. Several previous studies, including a North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) review of pretransplant dialysis status and graft outcomes, have described a potential correlation of peritoneal dialysis (PD) and graft thrombosis. This issue is of particular concern for pediatric transplant programs as more than 65% of children with end stage renal disease are treated with PD. We reviewed 7247 pediatric renal transplants performed between 1987 and 2001. Thrombosis was the cause of graft loss in 2.7% (199) of all the transplants performed. Among failed transplants, thrombosis was the third most common cause of graft loss in both index (11.6%) and subsequent transplants (14.5%). Thrombosis becomes the most common cause of graft failure (21%, 61/294) if one looks at transplants in the later cohort, from 1996 to 2001. This change is primarily because of a decrease in the incidence of acute rejection. In the PD group, 3.4% of all grafts were lost as a result of thrombosis. This compares with 1.9% in the hemodialysis group, 2.4% in the pre-emptive transplant group, and 4.1% among patients who received both dialysis modalities. There was a statistically significant difference in thrombosis failure risk in the different dialysis groups (p = 0.005) with those who received only peritoneal dialysis having the highest risk. Additional significant risk factors for graft thrombosis included; cadaver donor source (p < 0.001), cold ischemia time >24 h (p < 0.001), history of prior transplant (p < 0.001), donor age <6 yr (p < 0.001), and >5 pretransplant blood transfusions (p = 0.02). Using stepwise proportional hazards modeling, only pretransplant peritoneal dialysis, >24 h cold ischemia time, prior transplant, and donor age <6 yr were simultaneously associated with an increased risk of thrombosis. We conclude that pretransplant PD is associated with an increased risk of graft thrombosis. Special precautions should be undertaken in pediatric renal transplant patients who have received PD, especially infants and young children.     

Excellent outcome in infants and small children with thrombophilias undergoing kidney transplantation

One of the most common causes of early graft failure in children undergoing renal transplantation is vascular thrombosis. Numerous risk factors for graft thrombosis have been previously described. Children with various types of thrombophilias such as protein C, protein S and factor V Leiden deficiencies are at an increased risk for vascular thrombosis. Infants and small children with these disorders undergoing renal transplantation have not been well documented in the literature. We reviewed our experience in the diagnosis, peri-operative management and follow up of these patients at our institution. A retrospective analysis of all children undergoing renal transplantation at our institution, using data obtained from the Pediatric Transplant Registry at our institution since May 2000 was performed. The indications for renal transplant included focal segmental glomerulosclerosis, renal dysplasia and reflux nephropathy. One patient had factor V Leiden mutation and two patients had protein S deficiency. Patients were anticoagulated in the peri-operative and post-transplant period. All index transplants were performed with living donor kidneys. There were no adverse outcomes in children with thrombophilias despite having significantly lower weight at the time of transplant vs. children without thrombophilia. The incidence of graft thrombosis in the pediatric renal transplant recipients is high. We identify a potential cause of thrombosis in children not well documented in the literature. A high index of suspicion combined with preoperative screening and diagnosis of thrombophilias and an appropriate treatment plan may decrease the incidence of graft thrombosis in infants and small children undergoing renal transplantation.     

Rabbit antithymocyte globulin related decrease in platelet count reduced risk of pediatric renal transplant graft thrombosis

Graft thrombosis is a serious complication in pediatric renal transplantation. We assess a potential protective effect for the decrease in platelet count associated with RATG therapy against pediatric renal transplant graft vascular thrombosis. Between January 1986 and December 1998, 120 kidney transplants were performed in 95 pediatric recipients. Patients were divided into two groups. Group 1 (n = 61), non-RATG group received cyclosporine, azathioprine and steroids, while group 2 (n = 59), RATG group, received in addition, RATG at day 1 and continued for 4-10 days postoperatively. Platelet count prior to transplant, median change in absolute platelet count at 1 and 3 days post-transplant was recorded. Graft thrombosis incidence was examined. Six grafts (5%) developed thrombosis. All were in group 1 (p = 0.028). Median pretransplant platelet count (x10(9)/L) in group 1 was 283 vs. 280 in group 2 (p = 0.921). Median decrease in absolute platelet count (x10(9)/L) from pretransplant levels at one and three days post-transplant for group 1 and 2 was 18 vs. 83 (p 相似文献   

Outcome of kidney transplantation in Canadian Aboriginal children in the province of British Columbia

Abstract:  Renal transplantation remains the therapy of choice for children and adolescents with ESRD. Differences in graft survival are observed in kidney transplant recipients of different race and ethnicities. Data in pediatric populations are limited and confounded by disparities in access to health care. We performed a retrospective single Canadian centre database review to determine the short- and long-term outcomes of kidney transplantation in Aboriginal children compared to non-Aboriginals. A total of 159 primary renal transplant recipients at BCCH between 1985 and 2005 were examined (15% Aboriginal). Aboriginal children had different etiologies of ESRD, and a higher percentage of females, but were similar in age at transplantation, cold ischemia time and living donation rate. Early graft outcomes such as delayed graft function, episodes of acute rejection in the first year post-transplant and estimated glomerular function rate at one yr were similar in both groups. Long-term graft survival, however, was significantly worse in the Aboriginal group, with a significantly increased rate of late rejections: 50% compared with 26.7% among non-Aboriginals (p = 0.03). In a province with uniform access to health care, significant differences in long-term graft outcome exist among Aboriginal children compared with non-Aboriginals.     

Mycophenolate mofetil suspension in pediatric renal transplantation: three-year data from the tricontinental trial

Mycophenolate mofetil (MMF) is widely used to prevent acute rejection in adult solid organ transplant recipients, but data in children and adolescents are scarce. This prospective, multicenter, open-labeled, single-arm study investigated the efficacy and safety of an MMF-based immunosuppressive regimen in 100 pediatric renal transplant recipients over a 3-yr period of time. Three age groups were formed (<6 yr, n = 33; 6 to <12 yr, n = 34; 12-18 yr, n = 33). Basic immunosuppression consisted of MMF (600 mg/m(2) b.i.d), cyclosporin A microemulsion and corticosteroids. Seventy-three percent of patients were given anti-lymphocyte antibody induction therapy, of whom 74% received anti-thymocyte globulin. Patient and graft survival 3 yr after transplantation amounted to 98 and 95%, respectively. Twenty-five percent of all patients suffered a biopsy-proven acute rejection episode in the first 6 month post-transplant. Children undergoing induction therapy exhibited a numerically lower rejection rate (21 vs. 37%, p = 0.11). Three years after transplantation, the acute rejection rate added up to 30% (26% with induction therapy vs. 41% without induction therapy, p = 0.21). The number of patients with acute rejection was lowest in the youngest age group (18%), in comparison with 39% in the 6 to <12 yr and 33% in the 12-18 yr age group, respectively. For the entire patient population, the rate of patients who withdrew prematurely because of adverse events was low (12%). The present study shows that MMF therapy in pediatric renal transplant recipients leads to an excellent patient and graft survival 3 yr post-transplant with an acceptable safety profile.     

Mycophenolate mofetil in pediatric renal transplantation: non-induction vs. induction with basiliximab

North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) reports have shown anti-T cell antibody, OKT3, to be deleterious in pediatric renal transplant recipients treated with mycophenolate mofetil (MMF). Unlike OKT3, basiliximab is a chimeric monoclonal antibody to the alpha subunit of the interleukin-2 receptor on activated T-lymphocytes. We sought to examine the outcome of MMF with or without basiliximab induction therapy in pediatric renal transplantation. Between January 1998, and June 2001, 49 pediatric renal transplants were performed at our center and 41 met the criteria for this study. We retrospectively analyzed the records of 25 patients who received MMF, Prednisone, CSA or TAC, alone (group I) and 16 patients who received MMF, CSA or TAC, and Prednisone in combination with basiliximab (group II). The two groups were similar with respect to recipient or donor age, gender, ethnicity, donor source (LD vs. CAD), cold ischemia time, and primary diagnosis. The basiliximab group had a shorter follow up period because of its more recent addition to our pediatric immunosuppression protocol, 12.9 +/- 5.9 months vs. 35.5 +/- 7.2 months for group I (p < 0.0001). At 6 months, the acute rejection rate was 16% (group I) compared with 25% (group II) (p = 0.689). The patient and graft survival at 6 and 12 months were 100% respectively for both groups. Basiliximab was well tolerated without significant adverse events. At 6 months, there was no significant difference between the groups in the incidence of urinary tract infection or cytomegalovirus infection. These data suggest that in the short-term, MMF with or without basiliximab induction therapy appears to yield excellent and statistically similar outcomes. However, further controlled studies are necessary to verify these findings as well as to define the role of basiliximab in MMF-treated pediatric renal transplant recipients.     

Safety and efficacy of prolonged cytomegalovirus prophylaxis with intravenous ganciclovir in pediatric and young adult lung transplant recipients

CMV infection causes morbidity and mortality after transplantation. Despite a wide range of prevention strategies among pediatric lung transplant programs, the optimal duration of prophylactic therapy against CMV infection in pediatric lung transplantation is unknown. To assess the feasibility, safety, and short-term efficacy of extending intravenous ganciclovir administration from six wk duration to 12 wk duration in pediatric lung transplant recipients. An open-label pilot study was performed in primary pediatric lung transplant recipients with donor and/or recipient CMV seropositivity. Intravenous ganciclovir was given for 12 wk post-transplantation. Subjects were tracked for protocol completion. Toxicities monitored included renal dysfunction, myelosuppression, gastrointestinal and neurological complications, as well as infection related to indwelling catheter placement. Serial CMV levels were measured to determine short-term efficacy of the intervention. Nine of nine subjects enrolled completed the pilot study. Subjects' ages ranged from six to 18 yr. Indications for lung transplantation included cystic fibrosis (n = 7), idiopathic pulmonary hypertension (n = 1), and complex congenital heart disease with pulmonary hypertension (n = 1). Seven subjects underwent deceased donor bilateral lung transplantation and two subjects underwent heart-lung transplantation. No subjects had protocol-defined drug toxicity. No episodes of neutropenia, thrombocytopenia, or renal toxicity occurred. Five subjects had catheter-related infections (three after week 12 of ganciclovir). Seven of nine subjects had CMV detected by PCR (four prior to ganciclovir completion) with only one subject having a positive viral culture for CMV viremia (prior to ganciclovir completion). No subjects had UL-97 mutation for ganciclovir resistance detected. The use of prolonged prophylactic administration of ganciclovir for 12 wk duration is a feasible, safe, and effective treatment to prevent CMV viremia based on viral culture in at risk pediatric lung transplant recipients. Further clinical studies are underway to determine optimal CMV prevention strategies.     

Risk factors for cardiovascular disease in pediatric renal transplant recipients

About 1,000 children develop end-stage renal disease (ESRD) each year in the United States and about 5,000 children are currently receiving dialysis. Children who develop ESRD are eligible to receive renal replacement therapy, including renal transplantation. There are inherent risks associated with transplantation, including renal insufficiency, infections, post-transplant lymphoproliferative disorder, and cardiovascular disease (CVD). Potential risk factors for CVD in pediatric renal transplant recipients include renal insufficiency, hyperlipidemia, hyperhomocysteinemia, inflammation, malnutrition, anemia, and hyperglycemia/insulin resistance. Despite evidence that many children may possess various risk factors for CVD post-renal transplantation, there are very few studies that have attempted to assess the link between these risk factors and CVD in pediatric renal transplant recipients.     

Prevalence of renal dysfunction in tacrolimus‐treated pediatric transplant recipients: A systematic review

Renal dysfunction after non‐renal transplantation in adult tacrolimus‐treated transplant patients is well documented. Little is known about its prevalence in children. Age‐related changes in both disposition and effect of tacrolimus as well as renal function may preclude extrapolation of adult data to children. To systematically review the literature on renal dysfunction in non‐renal pediatric transplant recipients treated with tacrolimus. PubMed/Medline, Embase, and Google were searched from their inception until April 19, 2012, with the search terms “tacrolimus,” “renal function,” “transplantation,” and “children.” Eighteen of 385 retrieved papers were considered relevant. Twelve dealt with liver, four with heart transplant, one with heart and lung transplant, and one with intestinal recipients. Reported prevalences of mild and severe chronic kidney disease ranged from 0% to 39% and 0% to 71.4%, respectively, for liver, and from 22.7% to 40% and 6.8% to 46%, respectively, for heart and/or lung transplant recipients. Ranges remained wide after adjusting for follow‐up time and disease severity. Possible explanations are inclusion bias and definitions used for renal dysfunction. A considerable proportion of pediatric non‐renal transplant patients who receive tacrolimus‐based immunosuppression, appear to suffer from chronic kidney disease. This conclusion warrants further research into the real risk, its risk factors, and individualization of immunosuppressant therapy.     

Pediatric renal transplantation: single center experience

Although renal transplantation (RTx) is actually the first choice of treatment for children with end-stage renal disease, the number of transplanted children remains low in comparison with adults. The experience of the individual pediatric transplant center is very important in the outcome of pediatric transplant recipients. In this study, our pediatric renal transplantation experience is presented. We retrospectively analyzed the results of 72 pediatric renal transplants performed at Ege University Pediatric Nephrology Transplantation Center between June 1989 and May 2003. They were 40 girls, 32 boys and their mean RTx age was 13.27+/-3.73 yr (range 3-20 yr). Thirty-eight (52.8%) of the transplanted kidneys came from a living related donor, and 34 (47.2%) from a cadaveric donor. Preemptive RTx was performed in one patient and a second RTx was performed in one patient after two-period hemodialysis. Hypertension (31.9%), acute rejection (27.8%) and chronic rejection (13.9%) were the most common complications. Cytomegalovirus (CMV) infection occurred in 15 children (20.8%), none of whom died or lost their graft as a result of the infection. Pretransplant acquired hepatitis C virus (HCV) infection was detected in 12 patients (16.7%). Urinary tract infections (UTIs) were seen in 31 (43.1%) recipients. The 1, 5 and 10 yr graft survival rates were 91, 84 and 77%, respectively, and corresponding patient survival rates were 97, 84 and 77%, respectively by Kaplan-Meier method. The graft and overall survival was not correlated with sex, donor type, treatment modality, acute rejection episodes, hypertension, UTIs, CMV and HCV infection.     

Alternate day corticosteroid therapy and growth in renal transplant children

Corticosteroid therapy is probably the main factor inducing stunted growth in pediatric renal transplant recipients. Results of a randomized study in 35 children who received their kidney between 1981 and 1984 are reported. All patients had normal renal function and were taking azathioprine and prednisone to ensure immunosuppression. Eighteen months after transplantation, patients with normal renal biopsy results were randomized to receive further daily corticosteroid therapy (group A) for an additional year or to alternate-day corticosteroid therapy (group B). Chronologic age, bone age, renal function, and previous growth retardation were strictly comparable, in the two groups. During the first year, only prepubertal children in group B exhibited catch-up growth. In children undergoing puberty, annual statural gain was greater in group B (5.6 cm versus 3.2 cm in group A: p less than 0.001). Group A children were switched to alternate-day corticosteroid therapy one year after initiation of the study and exhibited improved growth after this change. No patient had renal function deterioration under alternate-day corticosteroid therapy, throughout the study period. Alternate-day prednisone should be offered to pediatric renal transplant recipients with satisfactory renal function as a mean for protecting growth potential.     

The outcome of pediatric cadaveric renal transplantation in the UK and Eire

An analysis of all pediatric cadaveric renal transplant recipients in the UK and Eire was undertaken to review the outcomes of pediatric cadaveric renal transplantation and to consider the implications for organ allocation procedures for pediatric recipients. Factors influencing the outcome of 1,252 pediatric cadaveric renal transplants in the UK and Eire in the 10-yr period from 1 January 1986 to 31 December 1995 were analyzed by Cox proportional hazards regression, including analysis of four distinct post-transplant epochs (0-3 months, 3-12 months, 12-36 months, and beyond 36 months). At the time of analysis (December 2000), 113 (11%) recipients had died and 47% of grafts had failed. In the multi-factorial modelling, the factors significantly affecting transplant outcome were cold ischaemia time, donor and recipient age and human leucocyte antigen (HLA) matching. Epoch analysis demonstrated that these factors operated at different times post-transplant. Cold ischaemia time had a strong influence on outcome at 3 months. A highly significant increased risk of graft failure was associated with donors under 5 yr of age. Young recipients had an increased risk of failure in the short term, but beyond 1 yr post-transplant there were few failures in young recipients while a steady rate of graft loss persisted in the older children. In terms of HLA matching, the worst outcome was observed for two HLA-DR mismatched grafts, while 000 and favorably matched kidneys (100, 010, 110 HLA-A, -B, -DR mismatches) survived longest. Hence, a policy of exchanging organs on the basis of HLA matching is justified for 000 mismatched and favorably matched kidneys. The poor outcome associated with very young donors should discourage pediatric units from transplanting kidneys from such young donors. The reasons for late losses in older recipients need investigation.     

Efficacy and tolerability of interleukin-2 receptor blockade with basiliximab in pediatric renal transplant recipients

Rejection remains a major threat in pediatric renal transplantation (Tx), causing graft failure and increased exposure to drugs. The new chimeric antibody, basiliximab, directed against the alpha-chain of the interleukin-2 receptor (IL-2R), has been shown to be effective in preventing rejection episodes in adult renal transplant recipients. In our single-center experience from Essen, Germany, we evaluated prospectively the efficacy and tolerability of basiliximab, in combination with cyclosporin A (CsA) and prednisone, in 38 unselected pediatric patients. Mean patient age at Tx was 10.1 yr. Twenty-eight children received a cadaveric organ and 10 children received living-related donor grafts. The 1-yr patient survival rate was 100% and the 1-yr graft survival rate was 95% (36/38 patients). No graft was lost as a result of immunological factors, and single rejection episodes were observed in eight patients (21%). Two of these rejections were steroid-resistant and responded to tacrolimus rescue therapy. The rate of infections was not enhanced; overt cytomegalovirus (CMV) disease was observed in two patients only. Malignancies have not been seen to date. The blockade of the alpha-chain of the IL-2R lasted for up to 6 weeks. We conclude that the addition of basiliximab to standard immunosuppression in pediatric renal transplant recipients is well tolerated and results in a low incidence of rejection. The simple mode of application and the lack of side-effects make basiliximab an especially useful adjunct in pediatric patients.     

Long-term results of basiliximab induction immunosuppression in pediatric liver transplant recipients

It has been shown that an induction therapy with the monoclonal anti-interleukin-2 receptor antibody basiliximab (Simulect) is capable to reduce the incidence of acute graft rejection in adult and pediatric liver transplantation (Ltx). However, data on long-term results using basiliximab in children post-Ltx are still pending. Therefore, the objective of our study was to report on the long-term results of basiliximab induction therapy in pediatric liver transplant recipients. A total of 54 children received two single doses of basiliximab in addition to cyclosporine and prednisolone following Ltx. We analyzed the incidence of acute and chronic graft rejection that of post-transplant lymphoproliferative disease (PTLD), and patient and graft survival. The follow-up was 22-46 months. The historical control group (matched controls) consisted of 54 patients treated with a cyclosporine and prednisolone dual therapy. Patient survival was 53 of 54 in the treatment group and 51 of 54 in the controls. One patient was retransplanted in the treatment group vs. three patients in the control group. The incidence of acute graft rejection was 16.6% compared with 53.7% in the control group (p < 0.001), that of chronic rejection was comparable in both groups (one of 54 vs. one of 54). The incidence of steroid resistant rejection was four of 54 vs. six of 54 that of PTLD were one of 54 vs. zero of 54. There were no adverse effects observed, which could be related to the antibody treatment. We conclude that basiliximab provides safe and effective induction immunosuppression in pediatric liver graft recipients. Short- and even long-term results are excellent.     

Neurophysiologic changes in live related kidney transplant children and adolescents

Uremic neuropathy is one of the most debilitating symptoms associated with end stage renal disease. In adults the only potential cure for uremic neuropathy is renal transplantation. No studies have investigated the neurophysiologic abnormalities among pediatric renal transplant recipients. The objective of this study is to describe the incidence, nature and factors affecting neurophysiologic abnormalities in young renal transplant recipients. Neurophysiologic study was performed for 31 of our live related pediatric renal transplant recipients; they were 21 males and 10 females. The mean age at transplantation was 13.2 +/- 3.1 yr. The neurophysiologic studies were performed at different time points after transplantation (range 12-60 months), with a mean period of follow-up after transplantation 3.2 +/- 1.1 yr. Electromyography of the following muscles was tested: abductor pollicis brevis of the thenar eminence, biceps brachii, extensor digitorum brevis and rectus femoris. The median and lateral popliteal nerves were tested for estimating the motor conduction velocity. Neuropathic changes were found in 19% of our cases with more affection of the distal muscles of lower limbs. Motor conduction velocities were reduced, distal latencies were lengthened, and motor unit action potentials were reduced or dispersed. The predictors for development of neuropathy by multivariate analysis were the cumulative steroid dose and graft dysfunction. These results suggest that neuropathy is prevalent among young pediatric renal transplants. The independent predictors for development of neuropathy are graft dysfunction and anemia. It is unclear how significant these findings are in view of absent clinical signs and symptoms. This may represent an early stage of a disease that is still silent.     

Pre-transplant blood transfusion and renal allograft outcome: a report of the North American Pediatric Renal Transplant Cooperative Study

Data from the North American Pediatric Renal Transplant Cooperative Study were analyzed to determine the effect of pre-transplant blood transfusions on graft survival and acute rejection for pediatric renal transplant recipients. Between January 1, 1987 and November 11, 1995, 4015 renal transplants in children <18 years of age (2007 living donor, 2008 cadaver) were registered in the study. Recipients were grouped by number of pre-transplant blood transfusions (0, n=1171; 1-5, n=1796; >5, n=1048). The risks of graft failure and acute rejection were related to number of pre-transplant transfusions by proportional hazards regression analysis. Models were adjusted for recipient age, sex, race, induction therapy, prior dialysis, prior transplant, HLA-DR mismatching, and transplant year. Additionally, the living donor (LD) model was adjusted for the use of donor-specific blood transfusion, and the cadaver donor (CAD) model was adjusted for donor age and cold storage time. The risk of graft failure was increased in LD (p<0.001) and CAD (p=0.001) recipients who received >5 pre-transplant transfusions. There was no significant difference in the causes of graft loss between groups. The risk of a first acute rejection decreased in LD recipients who received 1-5 blood transfusions compared with 0 (p=0.04) or >5 (p=0.003) and in CAD recipients who received 1-5 compared with 0 (p=0.05). We conclude that multiple (>5) pre-transplant blood transfusions are a risk factor for graft failure in pediatric recipients and should be avoided. However, limited blood transfusions (1-5) are associated with a decreased risk of acute rejection. Our data show that for pediatric recipients the number of pre-transplant blood transfusions is an important factor in transplant outcome.     

Peripheral blood biomarkers for the characterization of alloimmune reactivity after pediatric liver transplantation

Individualization of immunosuppressive medications is an important objective in transplantation medicine. Reliable biomarkers to distinguish between patients dependent from intensive immunosuppressive therapy and those where therapy can be minimized among pediatric transplant recipients receiving immunosuppressive medications are still not established. We evaluated the potential of cross‐sectional quantification of regulatory T cells, lymphocyte subsets, and cytokine concentrations as biomarkers in 60 pediatric liver transplant recipients with AR, CR, or normal graft function and in 11 non‐transplanted patients. Transplant recipients presenting with AR had significantly higher CD8⁺ T‐cell counts, significantly higher concentrations of IL‐2, and increased levels of IFN‐γ compared with asymptomatic patients or controls. Regulatory T‐cell numbers did not differ between children with rejection and children with good graft function. A tendency toward increased concentrations of IL‐4 and TGF‐β was detected in transplant recipients with good graft function. Cross‐sectional parameters of peripheral regulatory T cells in pediatric liver transplant recipients do not seem to be valuable biomarkers for individualizing immunosuppressive therapy prior to the weaning process. Lymphocyte subsets, IL‐2, IFN‐γ, IL‐4, and TGF‐β serum concentrations may be helpful to identify children in whom immunosuppression can be reduced or discontinued.     

Primary vascular thrombosis after renal transplantation in children

The aim of the study was to assess the incidence, causes, diagnostic and treatment modalities, and outcome of vascular thrombosis after kidney transplantation in children. Between 1984 and 1995 we performed 176 kidney transplants in pediatric recipients aged 1 to 18 years. Vascular thrombosis followed 7 transplants, 4 were renal vein and 3 arterial thromboses. Venous thromboses occurred 2 to 12 days after transplantation. All of the patients with a renal vein thrombosis lost their grafts. Arterial thrombosis developed in 2 cases of double renal arteries which were separately anastomosed into the recipient vessels. One graft was lost, but the other was saved by thrombolytic therapy (streptokinase). One child experienced intrarenal segmental artery thrombosis during acute vascular rejection, which resolved following combined anti-rejection and thrombolytic (intra-arterial streptokinase) treatment with full recovery of graft function. In all, vascular thrombosis complicated 7 out of 176 transplants (4.0%), and was the cause of 5 graft losses (2.8%). The incidence of vascular thrombosis was not increased in grafts with vascular anomalies (3/34 v. 4/142; p>0.05, chi sq.). We conclude that acute tubular necrosis, rejection and unstable volemia may predispose to vascular thrombosis. In selected cases, early diagnosis of vascular thrombosis may enable graft salvage by surgical or thrombolytic treatment.     

Impact of non-compliance on outcome after pediatric kidney transplantation: an analysis in racial subgroups

Renal transplantation is the therapy of choice for children with end-stage renal disease. Despite excellent patient survival, long-term graft survival is poor, especially in the African-American (AA) population. This article addresses non-compliance as a major cause of late-term graft loss in the pediatric population. Between July 1995 and September 2002, a total of 50 pediatric kidney transplants were performed at our institution. We have analyzed data for 44 of these kidney transplants. Twelve recipients were AA, 14 Caucasian (C) and 18 Hispanic (H). The remaining six patients of different racial origin were not included in this analysis. The mean age of the recipients was 10.9 yr (range 1.7-17.8). Thirty-one were cadaveric and 13 were living donor transplants. We analyzed creatinine level and graft and patient survival at 1, 3 and 5 yr post-transplant. Compliance was evaluated based on trends in cyclosporine levels, attendance to clinic visits, individual interviews and unexplained late graft dysfunction. One- and 3-yr patient survival rates were 100% for all racial groups, except the 3-yr patient survival rate for C, which was 86%. One and 3-yr graft survival rates for AA, C and H were 92 and 67%, 86 and 79% and 100 and 100%, respectively. However, at 5 yr, we found that AA recipients had a significantly higher rate of graft loss when compared to both H and C recipients (42 vs. 95 vs. 71%, respectively). Non-compliance was the main factor, accounting for 71% of cases of late graft loss. In conclusion, non-compliance is a problem of great importance in the pediatric transplant population, particularly in AA recipients, where it plays a major role in late-term graft loss.